We have examined factors affecting the in vitro differentiation of Pdx1(GFP/w) ESCs to pancreatic endocrine cells. Inclusion of Bone Morphogenetic Protein 4 (BMP4) during the first four days of differentiation followed by a 24-hour pulse of retinoic acid (RA) induced the formation of GFP(+) embryoid bodies (EBs). GFP expression was ...

The pancreas has a strong regeneration potential in mammals. Previous studies suggested that pancreas regeneration is correlated with proliferation and differentiation of pancreatic stem cells, but the field of pancreatic stem cells is still in its infancy. This study was undertaken to detect the expression of pancreas/duodenal homeobox-1 (PDX-1) and ...

The cytotoxic effect of trastuzumab in combination with oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2 (HER2)-overexpressing human pancreatic cancer cell line TRG in vitro and in vivo was investigated. HER2 expression in TRG was analyzed by RT-PCR and flow cytometry. For in vitro experiments, 5-fluorouracil (5-FU) was ...

Serotonin release from preloaded pancreatic beta-cells has been used as a marker for insulin release in studying exocytosis from single cells using the amperometric technique. We found that single pancreatic beta-cells exhibited oscillations in exocytosis with a period of 1-1.5 min as measured amperometrically by serotonin release. We also show ...

Misfolded proteins are recognized by the protein quality control and eventually degraded by the ubiquitin-proteasome system. Previously, we demonstrated accumulation of a misfolded non-glycosylated protein, namely proinsulin, in enlarged pre-Golgi intermediates and dilated rough endoplasmic reticulum (ER) domains in pancreatic beta-cells of Akita mice. In order to exclude effects possibly ...

Cellular models and culture conditions for in vitro expansion of insulin-producing cells represent a key element to develop cell therapy for diabetes. Initial evidence that human beta-cells could be expanded after undergoing a reversible epithelial-mesenchymal transition has been recently negated by genetic lineage tracing studies in mice. Here, we report ...

A number of studies have shown that pancreatic ductal adenocarcinoma develops through precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). PanINs are thought to initiate in the small ducts of the pancreas through activating mutations in the KRAS proto-oncogene. What remains unanswered is the identification of the individual cell type(s) that ...

The heterogeneity of salivary ductal cells, with regard to their sensitivity to Ca(2+)-mobilizing agonists, was visualized by multi-photon microscopy. Stimulation of isolated parotid ducts with 0.1 and 1 microM epinephrine (Epi) elevated the intracellular Ca(2+) levels ([Ca(2+)](i)) in approximately 30% and >90% of the ductal cells, respectively. Of the 0.1 ...

Most mechanistic studies of pancreatitis in mice employ the secretagogue-induced model. The currently reported studies were designed to develop an alternative, and possibly more clinically relevant, mouse model of pancreatitis. Na-taurocholate (10-50 microl, 1-5%) in saline, or saline alone, was retrogradely infused into the mouse pancreatic duct. The animals were ...

Pancreatic beta-cells are clustered in islets of Langerhans, which are typically a few hundred micrometers in a variety of mammals. In this study, we propose a theoretical model for the growth of pancreatic islets and derive the islet size distribution, based on two recent observations: First, the neogenesis of new ...

Pancreatic beta-cells show bursting electrical activity with a wide range of burst periods ranging from a few seconds, often seen in isolated cells, over tens of seconds (medium bursting), usually observed in intact islets, to several minutes. The phantom burster model [Bertram, R., Previte, J., Sherman, A., Kinard, T.A., Satin, ...

Several differentiation or morphogenic factors have known to be involved in the developmental process of endocrine pancreas. However, mechanism of action and functional relation of these molecules are not well elucidated particularly in beta-cell formation from adult pancreatic stem cells. We hypothesized that adult pancreatic stem cells could be activated ...

Three-dimensional (3D) cultures of epithelial cells offer singular advantages for studies of morphogenesis or the role of cancer genes in oncogenesis. In this study, as part of establishing a 3D culture system of pancreatic duct epithelial cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with pancreatic cancer cell lines. ...

The pancreatic adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression, and profound resistance to actual treatments, including chemotherapy and radiotherapy. At the moment, surgical resection provides the best possibility for long-term survival, but is feasible only in the minority of patients, when advanced disease ...

To test whether pancreatic duct cells are in vitro progenitors, they were purified from dispersed islet-depleted human pancreatic tissue using CA19-9 antibody. The purified fraction was almost entirely CK19+ with no insulin+ cells, whereas the unpurified cells (crude duct) were 56% CK19+ and 0.4% insulin+ of total cells (0.7% of ...

Blood glucose regulation has likely evolved during early vertebrate evolution to allow and secure the concurrent evolution of complex brains and nervous systems: an inner milieu of constant blood glucose levels through millions of years has provided an extra degree of freedom for the brain to evolve without having to ...

BACKGROUND: The shortage of islets for transplantation has led to find alternative insulin producing cells. Pancreatic progenitor cells in the duct have the potential to grow and differentiate into endocrine cells. In this study, we examined whether activin A can promote the expansion and/or differentiation of ductal cells into insulin-producing ...

Embryonic stem (ES) cells hold promise as a source for cell transplantation treatment of diseases such as type I diabetes. Further, cells releasing bioactive substances from ES cell progeny may be concentrated and purified for clinical applications. Although ES cell lines that express reporter genes have been established to isolate ...

Tissue plasticity is well documented in the context of pancreatic regeneration and carcinogenesis, with recent reports implicating dedifferentiated islet cells both as endocrine progenitors and as the cell(s) of origin in pancreatic adenocarcinoma. Accordingly, it is noteworthy that accumulating evidence suggests that TGFbeta signaling is essential to pancreatic endocrine development ...

ADAMTS9 is a secreted, cell-surface-binding metalloprotease that cleaves the proteoglycans versican and aggrecan. Unlike most precursor proteins, the ADAMTS9 zymogen (pro-ADAMTS9) is resistant to intracellular processing. Instead, pro-ADAMTS9 is processed by furin at the cell surface. Here, we investigated the role of the ADAMTS9 propeptide in regulating its secretion and ...

Endocrine cells in chick pancreas were observed to map their distribution during development and to perform morphometric studies starting on embryonic day 5. The ratio of exocrine to endocrine tissues first prevailed in favour of the endocrine ones, and changed abruptly after day 9 when rapid growth of exocrine tissue ...

It has been suggested that pancreatic acinar cells can serve as progenitors for pancreatic islets, a concept with substantial implications for therapeutic efforts to increase insulin-producing beta cell mass in patients with diabetes. We report what we believe to be the first in vivo lineage tracing approach to determine the ...

Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and ...

Curado Silvia S Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158-2324, - - 2007

Conditional targeted cell ablation in zebrafish would greatly expand the utility of this genetic model system in developmental and regeneration studies, given its extensive regenerative capabilities. Here, we show that, by combining chemical and genetic tools, one can ablate cells in a temporal- and spatial-specific manner in zebrafish larvae. For ...

The islets of Langerhans consist of endocrine cells embedded in a network of specialized capillaries that regulate islet blood flow. Despite evidence for a critical role of islet perfusion in endocrine pancreas function, there is information to support no fewer than three models of endocrine cell perfusion, emphasizing the lack ...

Orvis Grant D GD Program in Genes and Development, The University of Texas, Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, - - 2007

Regardless of their sex chromosome karyotype, amniotes develop two pairs of genital ducts, the Wolffian and Müllerian ducts. As the Müllerian duct forms, its growing tip is intimately associated with the Wolffian duct as it elongates to the urogenital sinus. Previous studies have shown that the presence of the Wolffian ...

Efforts to clone amyloidogenic proteins in the cells often have resulted in cell death. We report successful cloning and expression of recombinant human islet amyloid polypeptide (hIAPP) in cultured mammalian cells. Amylin gets secreted, forms fibrils that are toxic to target cells like beta cells of rat and human. The ...

Inflammatory injury to the pancreas results in regeneration of normal tissue and formation of metaplastic lesions of a ductal phenotype. These metaplastic ductal lesions (MDL) are called tubular complexes (TC), mucinous metaplasia, or pancreatic intraepithelial neoplasia. Because they are regularly found in chronic pancreatitis and pancreatic cancer, their formation is ...

Limited organ availability is an obstacle to the widespread use of islet transplantation in type 1 diabetic patients. To address this problem, many studies have explored methods for expanding functional human islets in vitro for diabetes cell therapy. We previously showed that islet cells replicate after monolayer formation under the ...

AIMS/HYPOTHESIS: Pancreatic islets have evolved remarkable, though poorly understood mechanisms to modify beta cell mass when nutrient intake fluctuates or cells are damaged. We hypothesised that appropriate and timely adjustments in cell number occur because beta cells release proliferative signals to surrounding cells when stimulated by nutrients and 'bleed' these ...

The vgf gene has been shown to be involved in several metabolic pathways. Because the pancreas is crucial to metabolism and food intake, we studied the VGF peptides in bovine, rat, and pig Langherans islets using antisera raised against specific sites along the primary sequence of the rat/mouse and human ...

Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation. In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation. Thus, cell number and ...

We previously presented evidence that proliferative human islet precursor cells may be derived in vitro from adult islets by epithelial-to-mesenchymal transition (EMT) and show here that similar fibroblast-like cells can be derived from mouse islets. These mouse cell populations exhibited changes in gene expression consistent with EMT. Both C-peptide and ...

The absence of efficient and directed methods for the differentiation of adult pancreatic progenitor cell populations to pancreatic islet cells has raised doubts concerning the regeneration potential inherent in the adult pancreas. Relatively low levels of islet cell differentiation have been reported using adult pancreatic cells in vivo and in ...

Insulin regulates glucose metabolism and activates cell growth. As the respiratory system is an alternative route for insulin administration in patients with diabetes mellitus, we studied the effect of insulin on rabbit tracheal airway smooth muscle (ASM) cell proliferation. We show that treatment of quiescent ASM cells with insulin for ...

Insulin injection therapy is the principal current treatment of type 1 diabetes. Patients, however, suffer from various complications generated by insufficient control of blood glucose levels over a long period. Therefore, a method which can infuse insulin in response to changes of blood glucose levels is eagerly desired. Transplantation of ...

'Bright Yellow 2' ('BY-2') tobacco (Nicotiana tabacum L.) suspension cells could not proliferate even with proper 2, 4-D concentration (0.6 mg/L) in the medium, when the initial cell density is low. However, the cells could divide and grow normally if conditioned medium (CM) was added to the medium, and the ...

OBJECTIVES: The aim of the current study was to investigate whether nicotine treatment would induce the proliferation of isolated rat primary pancreatic acinar cells in culture by activating mitogen-activated protein kinase (MAPK) signalling and exocrine secretion. MATERIALS AND METHODS: A nicotine dose- and time-response curve was initially developed to determine ...

Interactions between the endocrine cells in islets of Langerhans influence their secretory function, and disruption of islet structure results in impaired insulin secretory responses to both nutrient and non-nutrient stimuli. We have previously demonstrated that insulin-secreting MIN6 cells show enhanced secretory responses when grown as islet-like structures (pseudoislets) suggesting that ...

The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. ...

During organogenesis, the foregut endoderm gives rise to the many different cell types that comprise the hepatopancreatic system, including hepatic, pancreatic and gallbladder cells, as well as the epithelial cells of the hepatopancreatic ductal system that connects these organs together and with the intestine. However, the mechanisms responsible for demarcating ...

AIMS: Pancreatic islets can be lost early following allotransplantation from oxidative stress. Antioxidant enzyme overexpression could confer a beneficial effect on islets exposed to reactive oxygen species (ROS) and nitrogen species. Here, we tested the effect of MnTMPyP, a superoxide dismutase/catalase mimetic. METHODS: INS-1 insulin-secreting cells or human islets were ...

Resveratrol is a phenolic compound found in grape skins, mulberries, and certain nuts that has been shown to have antitumorigenic and anti-inflammatory properties. Macrophage inhibitory cytokine (MIC-1) is a member of the transforming growth factor beta (TGF-beta) superfamily that has been shown to have antitumorigenic activity and is up-regulated in ...

AIMS/HYPOTHESIS: Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes. MATERIALS AND METHODS: We obtained pancreatic biopsy ...

AIMS/HYPOTHESIS: Epithelium-mesenchyme interactions play a major role in pancreas development. Recently, we demonstrated that embryonic pancreatic mesenchyme enhanced progenitor cell proliferation but inhibited endocrine cell differentiation. Here, we investigated the role played by sulphated proteoglycans, which are known to be essential to embryonic development, in this inhibitory effect. MATERIALS AND ...

The systemic renin-angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic ...

The activation of c-jun N-terminal kinase (JNK) in pancreatic islets is associated with impaired function and viability, and JNK inhibitory peptides (JNKIs) are cytoprotective. In particular, l-isoforms of JNKIs were shown to improve islets viability, while the d-retroinverso isoform of JNKI (RI-JNKI), with a higher therapeutic potential due to longer ...